Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

OBJECTIVE: To explore the characteristics of differentially methylated genes and gene ontology associated with neural tube defects (NTDs). METHODS: Twelve subjects from 3 NTDs pedigrees were enrolled. Patients with NTDs have served as the case group, while their family members with normal phenotypes have served as the control group. Genomic DNA was extracted from peripheral venous blood samples of the families and used for DNA methylation analysis. Pairwise comparison was carried out primarily for patient-offspring pairs, and co-segregation of methylation pattern with NTDs was analyzed. Pathway related to differentially methylated genes was predicted with DAVID software. RESULTS: Pairwise comparison indicated that VTRNA2-1 was the only gene in which all CpG sites were methylated. Co-segregation of VTRNA2-1 gene methylation with NTDs was found in all pedigrees. Pathways of hypermethylated genes included plasma membrane component, regulation of cellular protein metabolic process, and regulation of actin cytoskeleton organization, while the pathways of hypomethylated genes have included transcription regulator activity, cell adhesion, and neuronal differentiation. CONCLUSION Methylation of the VTRNA2-1 gene has co-segregated with NTDs in the studied pedigrees. The pathways of differentially methylated genes has involved with mechanism of neural tube development.
CpG Islands ; DNA Methylation ; Gene Ontology ; Humans ; MicroRNAs ; genetics ; Neural Tube Defects ; genetics ; Pedigree

OBJECTIVE: To detect pathogenic variation in a pedigree affected with hereditary spastic paraplegia type 31 and explore its molecular pathogenesis. METHODS: Customized Roche NimbleGen capture probes were used to capture all exons of the target genes in relation with hereditary spastic paraplegia. The DNA samples were also assayed with fluorescent quantitative PCR as well as chromosomal microarray analysis using CytoScan HD chip. RESULTS: The proband and her father and grandfather were found to carry a deletion for position 85 992 693-86 842 693 on chromosome 2, which spanned approximately 900 kb and encompassed the REEP1 gene. The latter has been specifically associated with hereditary spastic paraplegia type 31. The same deletion was not found in her mother who is phenotypically normal. CONCLUSION The deletional variation of the REEP1 gene probably underlies the disease in this pedigree.
Female ; Humans ; Membrane Transport Proteins ; supply & distribution ; Paraplegia ; Pedigree ; Sequence Deletion ; Spastic Paraplegia, Hereditary ; genetics

OBJECTIVE:To study the clinical effects of curettage under hysteroscopy combined with estrogen and progesterone in preventing intrauterine adhesion after missed abortion.METHODS:A total of 120 patients receiving missed abortion selected from gynecology department of our hospital during Jun.2014-Jun.2016 were randomly divided into observation group (60 cases) and control group (60 cases) according to seguential coding.Observation group was given estradiol valerate 3 mg,qd,for 5 d in total,received curettage under hysteroscope,and was given Estradiol valerate tablet/Estmdiol valerate cyproterone tablet one tablet,qd after surgery,for 21 d.Control group received routine curettage and didn't take estrogen and progesterone during the perioperative period.The time of vaginal bleeding,endometrial thickness 14 d after surgery,the amout of vaginal bleeding with in 3 months after surgery,intrauterine adhesion,the occurrence of ADR were observed in 2 groups.RESULTS:In observation group,57 cases completed the study except that 2 cases withdrew from the study due to the amount of vaginal bleeding as much as menstrual volume and 1 case withdrew from the study due to pregnancy tissue self-discharge.The duration of postoperative vaginal bleeding was (3.2 ±1.1) d in observation group and (5.4 ± 1.9) d in control group.The endometrial thickness of observation group was (8.04 ± 1.52)mm and that of control group was (5.27 ± 2.36) mm;the incidence of intrauterine adhesion was 3.5％ in observation group (2/57)and 15％ in control group (9/60).Above indexes of observation group were better than those of control group (P＜0.05).CONCLUSIONS:Curettage under hysteroscope combined with estrogen and progesterone helps to reduce post-curettage vaginal bleeding,promote endometrial repair and prevent intrauterine adhesion so as to protect women's reproductive ability.

Objective To investigate the change of bone mineral density(BMD) in the early postpartum period and non-pregnant healthy women with the same age.Methods The American GE company's dual energy X-ray BMD instrument(DXA) was used to conduct the BMD detection at lumbar spine and femoral neck of 1 055 cases of postpartum women and 889 non-pregnant women.The subjects were grouped according to different ages and body mass index(BMI).Then the BMD value in each group was calculated and the results were statistically analyzed.Results The lumbar spine and femoral neck BMD values in difference age groups of the postpartum women appeared decrease as compared with the non-pregnant women group,the difference was statistically significant in the lumbar spine(P＜0.05).Conclusion BMD of early postpartum women in Chongqing area is significantly decreased.

Objective To investigate the correlation between neural tube defects (NTDs) and DACT1 gene, and provide the basic data for disease diagnosis and genetic counseling. Methods Blood samples were obtained from 163 NTDs patients and 480 unrelated healthy individuals. Mutation detection of DACT1 gene and DNA direct sequencing was carried out by PCR amplification. Bioinformatics analysis of these mutated loci was performed. Results Six mutations were found in NTDs patients, including 4 missense mutations (p.R45W, p.D142G, p.N356K and p.V702G). But these mutations were not found in 480 healthy individuals. Three mutated amino acid residues (p.45R, p.142D and p.356N) were highly conservative in evolution, and the mutated carriers were female patients, and suffered from anencephaly. Conclusion DACT1 gene mutation may be a risk factor of NTDs in Han population of northern China.

OBJECTIVE:To compare therapeutic efficacy and safety of chlorquinaldol-promestriene and miconazole nitrate for simple vulvovaginal candidiasis (VCC).METHODS:In retrospective analysis,a total of 231 patients with simple VCC were divided into observation group (116 cases) and control group (115 cases).Observation group was given Chlorquinaldol-promestriene vaginal tablet (0.2 g) every night.Control group was given Miconazole nitrate suppositories (200 mg) every night.Both groups received a course of treatment,lasting for 7 d.Clinical efficacies of 2 groups were observed at the first and second recheck.The symptom relief time recurrence and ADR of effective patients were observed.RESULTS:There was no statistical significance in the total response rates of 2 groups at the first reexamination,as well as total response rates of 2 groups and symptom relief time of effective patients at the second reexamination(P＞0.05).At the second reexamination,reoccurrence rate of observation group was significantly lower than that of control group,with statistical significance (P＜0.05).There was no statistical significance in the incidence of ADR between 2 groups(P＞0.05).CONCLUSIONS:Chlorquinaldol-promestriene is similar to miconazole nitrate for VCC in therapeutic efficacy and safety,but chlorquinaldol-promestriene is better than miconazole nitrate in reducing recurrence rate.

Early tumor shrinkage( ETS) is defined as the reduction rate of tumor volume evaluated in ear-ly treatment.In recent years,mutiple studies have demonstrated that ETS predicted tumor prognosis well,it can be used as an important predictor of prognosis.Finding a predictor in the early phase of treatment can optimize treat-ment regimens and ameliorate the prognosis of tumor.We summarize the research progress of the relationship be-tween ETS and prognosis.

OBJECTIVETo evaluate the photodynamic therapy (PDT) against multi-antibiotic-resistant Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S.epidermidis) obtained from patients with chronic rhinosinusitis (CRS).

METHODSForty-five CRS patients who had been given medical treatment but still needed endoscopic surgery were included in this study. The mucus from middle meatus was collected from these patients during surgery, followed by separation of S. aureus and S. epidermidis and drug sensitive test. The strains which could form biofilm were selected. Light emitting diode (LED) array with a major wavelength of (633±10) nm was used as light source and 5-Aminolevulinic acid (ALA) was used as photosensitizer in this PDT experiment. The safe range of LED dose and ALA concentration which were not toxic to bacteria by themselves were confirmed, and then did PDT experiment on S. aureus and S. epidermidis. The data of bacterial colony forming unit were transformed to lgCFU before statistical analysis.The Graph Pad Prism 5 software was used to analyzed the data.

RESULTSThirteen S. aureus and 16 S. epidermidis were included in this experiment(from 45 patients), all of them were multi-antibiotic-resistant bacteria, and four of S. aureus and five of S. epidermidis could form biofilm in each group. In planktonic S. aureus experiment, the mean lgCFU was 8.32±0.31 in control group whereas the experiment group was 6.47±0.67 (t=9.01, P<0.01), and in planktonic S. epidermidis experiment the final data was 8.34±0.20 (control group) and 6.97±0.59 (experiment group) (t=8.84, P<0.01). In biofilm S. aureus experiment, the mean lgCFU was 8.68±0.05 (control group), 6.90±0.96(experiment group) (t=3.68, P<0.05); and in biofilm S. epidermidis experiment the data was 8.67±0.05 (control group), 7.29±0.61 (experiment group, t=5.07, P<0.01).

CONCLUSIONOur results demonstrated that ALA-mediated PDT on multi-antibiotic-resistant S. aureus and S. epidermidis from CRS patients was effective in vitro. Additional work defining if the PDT treatment would damage the nasal mucosa and further checking the effectiveness of PDT in vivo is still needed.

Aminolevulinic Acid ; therapeutic use ; Anti-Bacterial Agents ; Biofilms ; Drug Resistance, Multiple, Bacterial ; Humans ; Light ; Photochemotherapy ; Photosensitizing Agents ; therapeutic use ; Rhinitis ; drug therapy ; microbiology ; Sinusitis ; drug therapy ; microbiology ; Staphylococcal Infections ; complications ; drug therapy ; Staphylococcus

Acinetobacter Infections ; drug therapy ; Acinetobacter baumannii ; drug effects ; pathogenicity ; Adult ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Burns ; drug therapy ; microbiology ; Cefoperazone ; administration & dosage ; therapeutic use ; Humans ; Middle Aged ; Minocycline ; administration & dosage ; therapeutic use ; Retrospective Studies ; Sulbactam ; administration & dosage ; therapeutic use ; Thienamycins ; adverse effects ; therapeutic use ; Young Adult